Diagnostic Potential of Platelets Derived Selected Tumor Biomarkers in Hepatocellular Carcinoma

Abstract

Cancer is a word attributed to a group of diseases which have the characteristic abnormal growth of cells and exhibit the potential to invade the surrounding. Liver cancer is considered to be the sixth in number when ranking the deadliest cancers worldwide. Liver cancer can be of several types depending upon the place of its origin. Among all the types of liver cancer, hepatocellular carcinoma (HCC) is the most common type. The number of HCC cases per year are reported to be increasing due to several contributing factors. The main causative factor for its increasing prevalence is the late diagnosis of the disease at its advance stage. The methods used for detection of liver cancer include CT scan and tissue biopsy. The main drawback of these methods is that patient goes for these procedures when the disease has already progressed due to their high cost and invasive nature. This limitation further contributes in the prevalence of the disease. To overcome these limitations there is a need to shift towards a less invasive procedure which is both cost effective and has accuracy i.e. liquid biopsy. Liquid biopsy is currently approved for clinical practice for many cancers i.e. NSCLC (Non-Small Cell Lung Cancer) The aim of the study was to provide basis for the introduction of a non-invasive and effective procedure for HCC diagnosis. Platelets are thought to be the potential candidates for designing liquid biopsy leading to early HCC diagnosis. Platelets are enucleated type of cells found in blood which originate from megakaryocytes. They are very well known for maintaining homeostasis and the initiation of wound healing. Recently, an interaction of tumor cell and platelets has been reported via the transfer of tumor associated molecules. Abstract 6 This is often referred to as education of platelets. Tumor associated biomolecules activate the platelets in a specific way and cause the splicing of pre-mRNA in a unique manner. This specific mRNA repertoire, hence, has the capability to serve as a basis for diagnosis of cancer. In the present study mRNA repertoire of the platelets from HCC patients as compared to control was observed. Samples from the HCC patients were obtained from Holy family Hospital Islamabad. For the given purpose TGF-β, NF-κB, VEGF, AKT and PI3K were selected to serve as potential biomarkers. The selected genes are well known for playing role in tumor growth and dissemination. Transcriptional analysis of the selected genes depicted that in the platelets from HCC patients, the expression level of TGF-β, NFκβ, and VEGF was significantly increased by 2.48, 2.35 and 2.78 folds respectively. Whereas, a decrease of 0.6 and 0.65 folds was observed in AKT and PI3K respectively as compared to control. Significant alteration in mRNA levels of the selected biomarkers depicts their potential to be used as possible biomarkers for early diagnosis of HCC. These results in future could be utilized to develop a noninvasive procedure for early detection of HCC with high specificity.